Abstract

The efficacy of traditional sclerotherapy is limited; it is unable to prevent
the recurrence of varicose pathologies in the lower limbs, and frequently leads
to complications. It acts on the clearly pathological superficial vessels, which
represent merely the effect rather than the cause of the disorder.

Our aim is to permanently restore the entire perforating and superficial
circulation in the lower limbs. The physiopathology of the circulation in the
lower limbs reveals how this objective can be achieved by reducing the diameter
of the vessels and strengthening the vessel walls, thereby reducing their
excessive capacity and restoring valvular continence. Logically, this objective
cannot be achieved by means of an obliterative or ablative procedure, but only a
“regenerative” method. To this end, we have invented a new technique:
three-dimensional regenerative ambulatory phlebotherapy (T.R.A.P.). T.R.A.P. is
a “gentle”, non-obliterative form of “sclerotherapy” which extends to the entire
superficial and perforating network. The phenomenon that we call “regeneration”
involves fibrosis that is neither sclerotic nor obliterative. (according to
Blakeston Gould’s Medical Dictionary, 1979, “regeneration” means “the repair of
structures or tissues lost by disease or by injury). Histological examination
reveals reduced calibre of the lumen and consolidated the connective structure
of the treated vessels. T.R.A.P. is carried out by injecting a new
“regenerating” solution, sodium salicylate 6% in an alkaline hydroglycerin
vehicle, methodically in large total quantities (from 10.5 to 31.5 ml) into all
visible vessels, including those visualised by means of transillumination.
T.R.A.P. yields an aesthetic and functional result that cannot be achieved by
means of any of the techniques previously used by us, including surgical
procedures. The results obtained have proved to be stable after six years, thus
demonstrating the functional effect of the method.

Introduction

The complications, recurrences and scant efficacy of sclerotherapy are, in
our view, inherent in the obliterative concept on which the method is based.
This concept has been called into question by the creation of three-dimensional
regenerative ambulatory phlebotherapy (T.R.A.P.). T.R.A.P. constitutes a step
forward from traditional sclerotherapy, which mainly treats the effect of
valvular insufficiency, to a non-obliterative therapy that extends to the entire
superficial and perforating circulation, thereby treating the cause of the
disorder as well as its effect.

Figure 1. T.R.A.P. is the systematic three-dimensional injection of regenerative
solution into all vessels visible even by means of
transillumination.

T.R.A.P. uses a non-aggressive well-tolerated solution that exerts a constant
action and can be injected in large quantities. In an extremely complex system
of tubes, such as the venous circulation in the lower limbs, what could be more
rational and less invasive than to apply the proper therapy through the tubes
themselves?

Physiopathology and therapeutic strategy

The functional anatomy of the venous circulation in the lower limbs reveals
that the valvular insufficiency of the perforating veins and the ectasia of the
truncal veins, reticular veins, venules and telangiectasias are, except for rare
cases (mechanical obstructions, traumas, arteriovenous fistulas, congenital
angiopathies, excessive functional performance (1), prolonged exposure to heat
or sun, cortisone application, radiodermatitis, inflammation, chronic skin
disorders, etc) due to congenital miopragia of the vessel walls (1, 2, 3, 4, 5).
This condition is manifested under the influence of hemodynamic pressure, age,
hormones, posture, habits and numerous other pathogenic factors. Miopragia
involves, albeit to different degrees, the entire superficial and perforating
circulation. The progressive weakening of the walls of the vessels that connect
the superficial circulation with the deep circulation causes the valves to
become incontinent. The resulting anomalous pressure in the superficial
circulation causes the vessels to dilate, an effect which is first manifested in
those vessels whose anatomical structure is least resistant.
Valvular insufficiency is dynamic. Contraction of the so-called ‘peripheral
heart’, which is constituted by the leg muscles, generates the highest venous
pressure: up to 300 mm of mercury (6,7). This region, which is of strategic
importance for the correct functioning of the venous circulation, contains about
100 perforating veins (8), as well as the origin of the small saphenous vein. By
contrast, the valvular and ostial incontinence of the great saphenous vein is of
marginal importance with regard to pressure, since the hydrostatic pressure at
the ankle is 80/100 mm of mercury regardless of whether the valves are continent
or not (9,10). The valvular incontinence of the largest superficial vein has a
clinical significance only if it is associated to saphenopopliteal incompetence
and/or valvular insufficiency of the perforating veins. Indeed, cases have been
observed of subjects born without valves in the great saphenous vein who do not
manifest any disorder, while efficient valves have been found in the external
iliac vein of subjects suffering from varicose veins (11).

Variations in the expression of the disorder depend on blood pressure, on how
close to the surface the incontinent perforating veins are located, and on how
well the walls of the vessels affected by hypertension can withstand the
increased pressure. Indeed, if the reticular veins in an area subjected to
anomalous pressure easily become ectatic, then ectatic capillaries are less
likely to form. If the walls of the reticular veins are able to withstand the
increased pressure, a dense network of telangiectasias is more likely to form.
Telangiectasias form when the ectatic reticular veins are no longer able to
absorb the rapid pressure increases caused by muscular contraction.
Telangiectasias may form even in the absence of visible reticular veins if the
capillary network is directly connected to an incontinent perforating vein.
Telangiectasias frequently form even after sclerotherapy and ablative or
obliterative surgery on the large superficial veins (see Fig. 10). Venous
insufficiency therefore displays multiple clinical manifestations, but what is
evident is that the ectatic veins that can be seen with the naked eye and those
that can be seen only by means of transillumination represent the quantity of
blood that escapes from the deep circulation. The ectatic vessels therefore
constitute escape valves for hemodynamic hypertension. If we reduce this venous
network without treating the cause of the disorder, the pressure on the
superficial circulation will increase and the initial unsightly conditions will
soon be restored. The anatomical-physiological considerations outlined above,
and the fact that phlebectasias very often recur after traditional obliterative
sclerotherapy and ablative surgery, have prompted us to adopt a radically
different approach. The obliteration and ablation of visible varicose areas does
not work because it is conceptually wrong; it treats the effect of the disorder,
and rarely the cause. Even if obliterative techniques are applied to perforating
veins that appear incontinent on color-flow Doppler scanning, the problem will
not be solved and the progression of the disorder will not be prevented. Indeed,
hemodynamic alterations may be caused that give rise to new capillary (matting)
and venular ectasias; following the obliteration of a perforating vein, the
pressure on the superficial venous circulation determined by other incontinent
perforating veins that cannot be revealed by means of the instrumental
examinations available may increase and be manifested at the surface of the
skin.

Traditional obliterative sclerotherapy and surgical ablation do not respect
the anatomical and functional integrity of the circulation, nor do they correct
miopragia. They act exclusively on the full-blown aspects of the alteration in
venous circulation, while the disorder is sustained by perforating vessels which
reveal their insufficiency only when the patient runs or walks. Clearly then,
the insufficiency of even a small percentage of these vessels, which cannot be
revealed by means of the instruments available, can thwart any traditional
treatment and give the erroneous impression that ectatic veins can form without
a hemodynamic cause, apart from the causes listed above. Saphenectomy is
certainly three-dimensional. The improvement seen in patients following ablation
of the great saphenous vein largely depends on the ligature of the major
perforating veins and on the obliteration of the perforating veins that are
connected to it. Surgical ablation of the saphenous vein, however, is an
incomplete treatment which yields unpredictable results (12, 13, 14, 15, 16, 17,
18, 19) and, from our point of view, cannot be adopted as the therapy of choice
for insufficiency of the venous circulation in the lower limbs, in the majority
of cases. Saphenectomy yields long-lasting, good-quality results only in those
patients in whom the residual perforating veins are continent. Even in such
cases, however, the developmental aspects of the varicose disorder determined by
the miopragia of the vessel walls cannot be avoided. While fine-tuning T.R.A.P.,
we have noticed that saphenectomy patients need more sessions of phlebotherapy
in order to achieve optimum results. We may hypothesize that this is due to the
anatomical-functional alterations caused by the operation itself.

With regard to ambulatory phlebectomy, until now this has been justified only
by the absence of residual hyperpigmentation. Obviously, the availability of a
solution that does not generate permanent post-sclerotherapy hyperpigmentation
relegates this operation to the level of a second choice.
Since it is not conceptually possible to obliterate or remove the entire
superficial circulation together with all the perforating veins, some authors
have focused on treating the ectatic reticular veins; these, however, represent
the effect rather than the cause of the disorder.
For all of the above-mentioned reasons, we have created a method that is not
obliterative. Three-dimensional regenerative phlebotherapy. shifts the focus of
the therapy from the superficial ectatic vessels and some of the major
perforating vessels to the entire superficial and perforating circulation.
Rather than obliterating the vessel, it aims at reducing the caliber of the
lumen and thickening and strengthening the vessel walls. To describe these non-obliterative
fibrotic effects on the vessel wall, we have adopted the term “regeneration”.
This term has been chosen in order to highlight the fact that the vascular
structure is restored to its pre-phlebectasia condition. The result is that
normal vascular capacity is recovered and the circulation begins to function
properly again. This is in stark contrast to the concept of obliterative
sclerosis or ablative surgery endorsed by traditional therapy.

Given that the miopragia of the vessel walls involves the entire superficial
and perforating circulation, all the visible vessels must be injected, including
those visualized by means of transillumination. Moreover, the solution, which
obviously must not be obliterative, will need to be forced into the underlying
vessels.
On the basis of studies and experimentation on non-aggressive solutions, we
adopted a 6% solution of sodium salicylate in an alkaline hydroglycerin vehicle
(20). The 6% solution exerts a strengthening effect and can be injected without
risk at high individual or total doses. In addition to the “regenerative” 6%
solution, we also use a 10% solution, which is injected primarily in cases of
hemodynamic matting.
The traditional injection technique that we adopted with this and other
sclerosing solutions was not, however, capable of resolving severe and
moderately severe cases of the disorder. Even in the most favorable cases, the
result obtained was not sufficiently long-lasting. Six years ago, therefore, we
changed our approach and created T.R.A.P. The principal concepts that we
modified are outlined in Tab. 1

Tab.1

Sclerotherapy

Phlebotherapy

Obliterative action

“Regenerative” non-obliterative action

Highly inflammatory action

Slightly inflammatory action

Only clearly pathological vessels and the reticular veins connected
to ectatic venules and telangiectasias are injected

Systematic injection of all vessels visible even by means of
transillumination

Acts on the effect of the disorder

Acts on both the effect and the cause of the disorder, i.e. on the
entire superficial and perforating circulation

Injecting large amounts of solution

engenders risks

Injection of large amounts of solution is risk-free

Efficacy proportional to the concentration of the solution injected

Efficacy proportional to the quantity of solution injected

Several solutions or concentrations used according to the size of the
vessels: the larger the vessel, the higher the concentration

A single concentration (6%) is mainly used; the higher concentration
(10%) is reserved only for the treatment of residual telangiectasias and
matting

The solution is not forced into the underlying vessels

The solution is forced into the underlying vessels

The action is two-dimensional; telangiectasias and superficial veins;
in rare cases three-dimensional: main perforators. Three-dimensional
action is exerted in limited areas and does not extend to the entire
circulation

Three-dimensional action extends to the entire superficial and
perforating circulation

Pre-established amounts of solution are injected into telangiectasias

The amount of solution injected into the vessels is determined by the
resistance to the plunger of the syringe

The size of the vessels is important

The pressure of the vessels is important

Treatment generally begins at the top

Treatment begins at the bottom

Anti-platelet therapy is normally contraindicated

Anti-platelet therapy is mandatory

Complications arise even if the procedure is performed correctly

No complications if the procedure is performed correctly.

On the basis of the general concepts described above, it is clear that, in
order to treat pathological circulation, all the vessels, truncal veins,
reticular veins and telangiectasias need to be injected in order in the same
session, with the aid of transillumination. Indeed, these vessels constitute the
“gateway” through which the solution comes into contact with the walls of the
non-visible (perforating and communicating) vessels.

Tab. 2 General concepts

Why obliterate or remove the veins when they can be cured?

Treating the effect and not the cause cannot "cure" the veins

Two-dimensional techniques are not able to treat a three-dimensional
disorder

The size of the vessel is not important; the pressure is.

A disorder that extends to the entire venous circulation in the lower
limbs cannot be treated by acting only on a part of that circulation.

To treat a complex circulation, what can be better than introducing the
cure through the vessels themselves and letting it go where it has to go?

It is more sensible to prevent the formation of varices than to cure
them once they have formed.

The great saphenous vein is blameless.

Doppler is blind

In the treatment of varicose veins, the most important diagnostic tool
is the syringe

The efficacy of phlebological procedures is judged by means of
photographs taken “before and after”, and in terms of the persistence of the
result obtained

“Regenerative” solution

The sodium salicylate in an alkaline hydroglycerin buffered vehicle solutions
(********[1]) were formulated in 1992 and their formulae
were published in 1993 (21). Sodium salicylate was chosen because it has both an
anti-inflammatory and an anti-clotting effect. Its alkaline pH is useful in that
it limits the absorption of the salicylate, neutralizes its metabolites and
accelerates its excretion. The hydroglycerin vehicle slows down the flow of the
solution in the vein, thereby allowing the sodium salicylate to remain in
contact with the endothelium for a longer time. The viscosity of the solution,
in addition to retarding its dilution, enables complete contact to be made with
the intravascular surface, a feature that aqueous sclerosing solutions lack,
unless air is added. The use of foam, however, is an extreme measure in
obliterative sclerotherapy and is not suited to “regenerating” the circulation.
The glycerol contained in ******** slows down the absorption of the sodium
salicylate, further enhancing the safety of the solution. The fact that glycerol
exerts a preservative and anti-bacterial effect means that, when it is used in
association with sodium salicylate, there is no need to use benzyl alcohol, as
other formulae do; allergic complications are therefore avoided (22).
The viscosity of the 6% solution is such that it facilitates injection into the
reticular and truncal veins, while the less viscous 10% solution facilitates
injection into the finest telangiectasias. In the case of reticular veins, the
viscosity of the solution enables it to be injected into the vessel lumen safely
and without aspiration. Consequently, a lower concentration of the active
ingredient is required to treat larger vessels, while a higher concentration is
used to treat smaller vessels (matting).

From 1992 to 1997, we used these solutions in a traditional manner.
They were very well tolerated, both locally and generally, and did not give rise
to any permanent hyperpigmentation, ulcers, marked or long-lasting edema or
post-sclerotherapy pain. Even today, in patients who do not wish to undergo
treatment of the circulation, we continue to use ******** in its three
concentrations (the 8% solution is obtained by mixing the 6% and 10% solutions).
Comparison between 0.5% polydocanol and 8% sodium salicylate in an alkaline
hydroglycerin buffered vehicle on both legs in 100 patients (23) revealed that,
for the same efficacy, the latter exerted a more constant action, caused fewer
side-effects and yielded a more rapid return to health.

The absence of marked inflammatory phenomena, and the very good
tolerability are particularly important in that they enable large
amounts of the solution to be injected.

The LD-50 of intravenous polydocanol in the dog is
50 mg/kg The LD-50 of intravenous
sodium salicylate in the dog is 562 g/Kg. In humans, concentrations of
salicylate greater than 200
mg/ml are regarded as toxic. In
mice, the LD-50 of glycerol administered intravenously is 6.0 g/Kg. It should be
stressed, however, that the alkalization of ******** makes the absorption of
sodium salicylate at the systemic level practically nil.

“Regenerative” fibrosis

We do not claim that the vessel fibrosis caused by sodium salicylate in an
alkaline hydroglycerin buffered vehicle is histologically different from that
caused by other chemical solutions. A non-buffered solution of sodium salicylate
and glycerol almost identical to 6% ******** has been tested on an ear vein of
the rabbit, producing a clinical and histological effect equivalent to that of
chromic glycerin (24). The author of that paper observed that this solution is
excellent in the treatment of telangiectasias of less than 1 mm. In comparison
with chromic glycerin, however, sodium salicylate in an alkaline hydroglycerin
buffered vehicle solution has the advantage of not containing trivalent
chromium, which is both irritative and allergenic (25), not least because it
contains nickel, which is present as an impurity in chromium salt (21).
Moreover, far higher doses of sodium salicylate in an alkaline hydroglycerin
buffered vehicle can be injected without untoward effects.

The histological specimens taken from one of our patients show the structural
effects exerted by 6% sodium salicylate in an alkaline hydroglycerin buffered
vehicle on large-caliber veins, the walls of which display a fibro-elastic
structure. The wall fibrosis induced by the endoluminal injection of the
solution causes thickening without disorganization of the wall; indeed, the
elastic fibers within the wall remain intact (Fig. 1).

Figure 1 (Left) Histological section of skin (fixed in 10% buffered formalin, paraffin embedded and routinely processed; Weigert stain; enlargement 20 X). Dermal venule of medium-large calibre. The structure of this type of venule is characterised by sparse elastic fibres – not organised into a true, continuous elastic lamina – in the context of fibrous connective tissue of the wall. The vessel (visible “in vivo” as a phlebectasia) has a large eccentric lumen. The wall displays a non-uniform thickness and disorganised layers at several sites, and is permeated by a scant inflammatory infiltrate consisting mainly of lymphoid and monocytoid cells. The endothelial lining lacks continuity. Sub-endothelial microvacuolation is also seen.
(Right) Histological section of skin. The same patient, the same area and a vein of equal size, seen after treatment with 6% sodium salicylate in an alkaline hydroglycerin buffered vehicle solution. Weigert stain; enlargement 20 X. The wall is of regular thickness. The internal endothelial layer is continuous. The wall shows no inflammatory infiltrate. Sodium salicylate in an alkaline hydroglycerin buffered vehicle solution treatment has restored uniform wall thickness, reduced the calibre of the lumen and consolidated the connective structure of the vessel wall. We have summarised these effects with the term “regeneration”.

The ability to cause controlled, predictable fibrosis, which is a feature of
sodium salicylate in an alkaline hydroglycerin buffered vehicle solution,, can
be verified by observing the superficial vessels. If small amounts of 6%
solution are injected into a vein, the caliber of the vein will be reduced
within a week. Further injection into the same vein will result in a further
reduction in caliber within another week, and so on until the vein is no longer
visible. If, by contrast, we inject enough of the solution to “regenerate” the
underlying vessels, the resulting reduction in hemodynamic pressure will allow
the vein to shrink until it is no longer visible after only one treatment
session. This does not mean that the vein has been obliterated. Obliteration is
accompanied by evident inflammation and by sclerotic hardening of the vessel.
The injection of ******** does not have such effects, even in large-diameter
reticular veins. Intravascular blood accumulation may occasionally occur during
T.R.A.P.. However, even in such cases, the vessel is not obliterated completely.

Indeed, if a vessel containing an accumulation of blood (and therefore
already treated) is erroneously re-treated, it will still be able to take in a
fair amount of solution, and the only indication that a vessel containing an
accumulation has been injected will be the quality of the blood that seeps from
the injection site. Intravascular accumulations of blood should be avoided as
far as possible, though one or two are acceptable. They may occur in large
superficial varicosities and in veins in which the blood flow is slow. They have
never occurred, and we think it unlikely that they may occur, in vessels in
which the blood flow is rapid, as in the perforating veins.

With regard to telangiectasias, it is irrelevant whether their disappearance
is due to obliteration or to “regeneration”, as long as they disappear. This is
not merely an esthetic consideration, as their disappearance indicates that
hemodynamic continence has been correctly restored. For what concerns the
ability to consistently induce efficacious fibrosis, we do not know whether this
feature is exclusive to sodium salicylate in an alkaline hydroglycerin buffered
vehicle solution or whether it can be achieved by means of other solutions. At
present, we know that chromic glycerin is able to produce a similar degree of
fibrosis, though we have never considered the possibility of injecting large
amounts of this solution. With regard to exclusively water-based solutions, we
believe that, if suitably diluted, they may be able to exert a “regenerative”
effect. However, we do not know whether they are able to maintain this effect in
depth, on starting from the superficial vessels, or whether they would
immediately become diluted and therefore lose all efficacy.

Patient assessment

All patients undergo anamnestic and vascular examination. A history of
thrombophilia warrants particular attention. In T.R.A.P., it is important to
observe the skin and subcutaneous tissues carefully in order to pick out all the
“gateways” to be injected. Of the 400 patients treated by us, solo il 10% had
already undergone color-flow Doppler scanning examination. This examination is
not important in the three-dimensional regenerative phlebotherapy. Indeed, in
the case of an exquisitely dynamic disorder that is manifested when the patient
is in movement, the diagnostic potential of color-flow Doppler scanning is
modest. This assertion is supported by Fig 2.27 of the treatise Sclerotherapy by
Mitchel P. Goldman (24), in which Doppler examination of a patient suffering
from a severe venous disorder does not reveal any impairment of the sapheno-femoral
or sapheno-popliteal junctions, nor any incompetence of the perforating veins.
To our way of thinking, this is completely absurd, in that even the tiniest
telangiectasia is the outward manifestation of the valvular incontinence of an
underlying vessel (26), except for those rare cases already mentioned. If we
consider that all the vessels that make up the venous network in the lower limbs
are interconnected (27), it is fairly obvious that valvular insufficiency may be
manifested in the superficial circulation. The permanent esthetic and functional
results of T.R.A.P. are achieved through the non-obliterative fibrosis of the
large and small incontinent perforators and the truncal veins, which may be
thought of as special superficial-perforating veins. It should be borne in mind
that most incontinent perforators are not visible on color-flow Doppler
examination. In any case, color-flow Doppler scanning was performed in all
patients presenting complex or painful disorders.

Technique

T.R.A.P. utilizes a 2.5 ml syringe, two or three 30 G ½ needles, the 6%
******** solution, 1% lidocaine chlorhydrate, cotton wool and disinfectant
(benzalkonium chloride).
Both the syringe and the needle must be standardized, as they are diagnostic as
well as therapeutic tools. Indeed, the operator is able to use the syringe to
assess the degree of incontinence of the vessels under treatment. Consequently,
the same syringe and needle are used to inject both truncal veins and
telangiectasias. When the needle is no longer able to penetrate easily into the
telangiectasias, it must be replaced. While a worn needle-tip is still able to
penetrate a vein, it will tend to displace rather than penetrate telangiectasias.

The lower limb is subdivided into three functional regions: medial, posterior
and lateral (Fig. 3).

Figure 3 The limb is divided into three functional regions: medial,
posterior and lateral.

First, the medial region of the foot, lower leg and thigh is injected; a week
later, the posterior region is treated, followed in the third week, by the
lateral region. During the fourth week, the first region is treated again, and
so on. If the disorder is mild, two regions, or even the entire limb, may be
treated in the same session. Once the skin has been disinfected, the 6%
solution, to which 0.5 or 1 ml of 1% lidocaine chlorhydrate without conserving
agents has been added inside a 3 ml vial, is injected. The addition of lidocaine
is useful on account of its analgesic, anti-inflammatory (28) and vasodilatory
action (29, 30).

The operator begins by injecting the phlebectatic
corona in the foot. In this area we add 1 ml of lidocaine to the 3 ml vial.
Working upwards towards the root of the thigh, the operator injects, in order,
all the vessels encountered. The operator begins by injecting the phlebectatic
corona in the foot. In this area we add 1 ml of lidocaine to the 3 ml vial.
Working upwards towards the root of the thigh, the operator injects, in order,
all the vessels encountered.

Figure 4
(Above) Phlebectatic corona. (Center) Immediately after the second
session of regenerative phlebotherapy.
(Below) Result after the third session.

Abb.5 Phlebektatische Krone vor und nach Phlebotherapie

This means that treatment begins in the area of the highest hemodynamic
pressure and ends in the area where hemodynamic pressure is lowest. In the
lateral region of the thigh, we now treat the veins first. This is in contrast
with the other regions, in which the veins and telangiectasias are treated at
the same time. Indeed, in the lateral region, injecting the telangiectasias has
a two-dimensional effect that is not encountered in the other regions; the
solution mainly spreads superficially rather than in depth. This engenders a
risk of matting on the part of an untreated incontinent perforator. Hemodynamic
matting is caused by incomplete treatment together with an excessive
concentration of solution.
This highlights the need to inject the solution in a way which is both orderly
and complete (all the “gateways”), from the regions of higher pressure to those
of lower pressure.

Moreover, in order to ensure that ******** exerts a constant
effect, it is also important to set the final concentration of the solution
accurately within a narrow range (from 0,5ml to 1ml of lidocaine per 3 ml vial).
The amount of solution to be injected and the area of surface whitening are not
predetermined. If the plunger of the syringe encounters firm resistance, a small
amount of solution is injected; if resistance is weak, the amount necessary to
regenerate the communicating vessels will be injected, up to a maximum of 2 ml.
The injected solution is swept along the vessels by firmly stroking the surface
of the skin with cotton wool soaked in benzalkonium chloride so that it comes
into contact with the largest possible area of the endothelial surface. The
solution always follows the path of least resistance, which is usually the deep
path. Normally, 0.5 ml of solution is enough to treat the perforating vessels in
the leg (31). The way that the operator can be sure that the tip of the needle
has penetrated the vessel is by gauging the resistance encountered by the
plunger of the syringe. The recent adoption of transillumination has solved all
our injection-related problems and has simplified the correct execution of the
technique. In the first treatment sessions, there is no need for the
telangiectasias to disappear.

Like the reticular veins, telangiectasias are merely "gateways" and remain
visible until the hemodynamic pressure in the region is reduced. Obliterating
the telangiectasias during the initial sessions does not constitute
phlebological therapy. Given that such an approach treats only the effect and
not the cause of the disorder, it must be regarded as purely cosmetic. Moreover,
if we do adopt this approach, we will for some time be prevented from treating
the incontinent perforating veins, which are the true cause of the disorder. The
three-dimensional concept is clearly illustrated by the fact that 1 ml of 6%
solution may be injected into an isolated telangiectasia 2 mm in length (21).
This means that the pressure on the plunger of the syringe is low and that the
telangiectasia is the superficial manifestation of the valvular incontinence of
an underlying vein that is directly connected to it (32) and which flows into
the deep circulation. The resistance felt on the plunger of the syringe is
therefore not related to the size of the visible vessel injected, but to the
size of the vessels connected with it. If the injection sites bleed, they are
momentarily covered with a swab of cotton wool soaked in benzalkonium chloride.
Within a few seconds, perivascular edema stops the bleeding. The operator must
learn to evaluate the speed at which blood issues from the injection sites, as
this is a valuable indication of the residual hypertension.

If this pressure is still high, treatment of the non-visible ectatic
circulation will have to be completed by injecting all the reticular veins in
the area involved, as well as the telangiectasias. Unlike traditional
sclerotherapy, in which the concentration of the sclerosing solution is usually
increased if the patient fails to respond well, T.R.A.P. deals with “difficult”
patients by increasing the amount of the solution injected. The recommended
limit of 31.5 ml of 5% solution is determined by the duration of the treatment
session, which is about 30 minutes, and by the need to keep well within the
safety margins: 31.5 ml of solution contains 27 ml of 6% sodium salicylate in an
alkaline hydroglycerin buffered vehicle solution plus 4.5 ml of 1% lidocaine,
which is sufficient to treat even the most severe cases. During experimentation
of the method, we injected up to twice this amount of solution (therefore 9 ml
of lidocaine) without any untoward effect. In that case, the amount of sodium
salicylate injected was 3.15 g and therefore still within the 3.6 g limit of
sodium salicylate used as a sclerosing solution (33, 34). The amount of
lidocaine that can be injected as an intravenous bolus in cardiac pathology is
100 mg, which is the equivalent of 10 ml of 1% lidocaine. Small quantities of
lidocaine diluted in a hydroglycerin vehicle and injected into different sites
in the peripheral venous system are extremely well tolerated. The LD-50 of
intravenous lidocaine in mice is 45.1 mg/kg.

During treatment, no sticking plasters are used. After treatment, the patient
remains immobile on the table for 2 or 3 minutes in order to allow the solution
to remain in contact with the vascular endothelium and to prevent rapid
dispersion of the solution into the circulation. In patients in whom the
disorder is severe, this period is extended to 5 or 10 minutes. This longer
period of immobility is adopted only after the first course of treatment
sessions carried out on the three regions of the same limb, and only after
hemodynamic improvement has been ascertained.

The saphenous veins also have to be regenerated by means of direct injection,
with the aid of transillumination or Doppler, and indirectly through their
collateral vessels. Once all the veins, venules and several of the
telangiectasias in one limb are no longer visible, the contralateral limb is
treated. After treatment, an anti-inflammatory product is applied to the area.
Before getting up, the patient puts on elastic stockings; in more severe cases,
these should also be worn for the first night. This elastic compression is
important, in that it prevents blood stasis, improves blood flow in the limb and
facilitates ‘regeneration’. It must be maintained for a few weeks after
completion of the treatment. All patients require anti-platelet therapy in order
to limit the accumulation of intravascular blood and prevent venous thromboses.
We administer 50 or 100 mg of acetylsalicylic acid or of a product of our own
formulation, composed of several vegetable extracts, vitamins and lipoic acid,
which exerts an anti-platelet, anti-homocysteine, chelating, anti-inflammatory,
hemorrheological and anti-free radical action. The anti-platelet action of this
preparation is achieved through the sub-active dosage of four extracts, which
act at four different points in the platelet-aggregation cascade (Angiovein).
Post-treatment edema lasts only a few hours, and ecchymoses generally no longer
than two or three weeks. The rare small sites of intravascular blood stasis are
pierced with the 30 G1/2 needle during the subsequent sessions.

If the patient has evident varicosity, bandages are used to compress the
large varices, in order to prevent intravascular blood stasis; they are also
used after injection of the evident phlebectatic corona in the foot.
Intravascular blood stasis is infrequent, and can be reduced even further by
reducing the concentration of the solution injected in patients with evident
varicosity; this is achieved by adding 1 ml (instead of 0.5 ml) of 1% lidocaine,
the same dilution used in the phlebectatic corona, to the 3 ml ampule of 6%
******** during the first three sessions of phlebotherapy. The slower blood flow
and the stasis determined by the ectasias enhance the efficacy of the solution.

Results

The effect of T.R.A.P. is clearly visible on the surface of the skin
(Fig.6-10).

Figure 6 Saphenectomised patient with evident phlebectatic corona and varices.
Result after “regenerative“ treatment of the right leg.

Aesthetic results can be classified at three levels: 1) vessels are no longer
visible when the limb is observed from a distance of 1.5 meters; 2) vessels are
no longer visible when the limb is observed from a distance of 50 cm; 3)
telangiectasias are no longer visible when the limb is observed under the
magnifying glass. Our recent adoption of transillumination also enables us to
verify the complete disappearance of the dilated reticular veins, which are not
visible without transillumination. The fact that a vessel can no longer be seen
does not mean that it has been obliterated. Rather, it indicates correct
shrinkage of the vessel, provided that the inflammatory and thrombotic phenomena
associated with obliteration are not manifested. The fact that the results
obtained seem to be permanent is the most convincing proof that functional
integrity has been restored. However, it must be borne in mind that the
permanent disappearance of telangiectasias and varices achieved by means of
T.R.A.P. depends on the reduction in hemodynamic pressure and the reactivity of
the vessel wall.

Figure 7 Varicose veins before and after

Figure 8 (Left) Patient who had never undergone any therapy. (Center)
Immediately after T.R.A.P. in the posterior region of the left leg, 28 ml of
solution have been injected. (Right) Result after three sessions of regenerative
phlebotherapy

Clearly then, if the capillaries are very fragile, complete disappearance of
the telangiectasias cannot be guaranteed. From the point of view of T.R.A.P.,
“difficult” patients are not those with very evident ectatic veins and
capillaries, much less those with one or two large varicose veins; rather, they
are patients in whom the vessel walls in the whole venous tree, from the veins
to the finest capillaries, display marked miopragia. Such patients present with
a fine network of visible ectatic venules and capillaries that take on the
appearance of red patches in which the anatomical structure of the capillaries
can no longer be discerned, even under a magnifying glass. In such patients it
is difficult to achieve a completely satisfactory esthetic result.

Figure 9 Patient under treatment with three-dimensional regenerative
phlebotherapy. The telangiectasias must not be obliterated; they form if the
reticular veins resist dilation. Regenerative treatment always begins with the
vessels in the foot. The regenerative solution is injected into all the
“gateways” that are visible either with the naked eye or by means of
transillumination, in a single region of a single limb. It is not necessary for
the telangiectasias to disappear during the first few sessions; they will
disappear once the three-dimensional regenerative treatment has normalised the
hypertension caused by the insufficiency of the non-visible veins. Restoring
normal blood pressure will cause the telangiectasias to disappear even though
the “regenerative” solution has no sclerosing action. The advantages of using a
non-obliterating solution are obvious: the treatment is rapid, does not give
rise to complications and does not cause the pain that typically follows
sclerotherapy.

With regard to
matting, we carefully treat the area with three-dimensional phlebotherapy
and inject the telangiectasias with 10% ********. The most difficult cases of
matting to treat are those with the highest pressure and those that arise even
after modest pressure increases in a context of very marked miopragia. If the
former cases were treated with a two-dimensional technique (laser and
sclerotherapy), matting would inevitably recur. The cases of inflammatory
matting resolve spontaneously and do not require treatment (inflammatory matting
is clearly visible when timedsurgical
de-epithelialisation at 1 Watt is performed on sites of recent
hyperpigmentation, as this reveals the dilated capillary-papillary plexus).

Figure 10: Extensive matting in a patient who had
undergone saphenectomy and subsequent obliterative sclerotherapy. This is the
most difficult situation to deal with on account of the serious iatrogenic
alterations to blood flow and the lack of “gateways” through which to regenerate
the underlying vessels. After phlebotherapy. regeneration.

Figure 11 Injection of a small perforating vein visualised by means of
transillumination. The syringe and the needle are perpendicular to the surface
of the skin.

Discussion

The fact that only a very small percentage of the people affected by venous
disorders currently undergo phlebological therapy is indicative of a widespread
lack of confidence in the treatments proposed. This lack of confidence stems
from the failure of traditional techniques to produce results that fulfill
patients’ expectations. Before the creation of T.R.A.P., our results were very
poor, even though for some years we believed that they were good. This was due
to the fact that poorly efficacious techniques had become consolidated, without
ever being subjected to a rational critique.

T.R.A.P. is a conservative technique for the functional and esthetic
treatment of venous insufficiency. It is easy to carry out and its results are
consistent and longer-lasting than those of any other technique that we have
used. In our view, this is the best indicator of the efficacy of the method.
After undergoing three-dimensional regenerative phlebotherapy, patients can
immediately return to their normal activities, without any untoward effects..
The use of a non-obliterating solution considerably reduces the risks of the
treatment. Over the six years of development of this technique, our utilization
of the sodium salicylate in an alkaline hydroglycerin buffered vehicle solution
has steadily improved. Cases of pigmentation are rare, limited to the injection
sites and short-lived; from the esthetic point of view they are therefore
irrelevant and, after the first session, are always avoidable. With regard to
matting, we maintain that the most critical areas are the internal region of the
knee and the lateral region of the thigh. Transillumination, which we have only
been using for the past year, has proved very useful in completing the
regenerative action in these areas and has enabled us to minimize this
complication, which, moreover, normally resolves easily. T.R.A.P. acts on the
entire superficial and perforating circulation; it therefore enables the source
of the problem to be treated and proper venous capacity to be restored, thereby
limiting recurrence of the disorder. Another advantage of using a
non-obliterating solution is that the valves, which are the most resistant
structures in the vessel (35), are not damaged. This contrasts starkly with what
happens during obliterative sclerotherapy, in which re-canalization almost
always gives rise to a valveless vessel. Owing to the characteristics of the
solution used, standardization of the syringe, and, especially, the use of
transillumination, injection of the poorly visible ectatic reticular veins,
which is troublesome when traditional sclerosing solutions are used, becomes
extremely easy. In our experience, the injection of large amounts of sodium
salicylate solution in a 6% hydroglycerin vehicle supplemented with lidocaine
has never caused any notable side-effects in patients. No post-therapy scotoma
has ever been recorded and tests for micro-hematuria and hemoglobinuria have
always proved negative. Moreover, pharmacokinetic testing has revealed that the
solution is totally eliminated after 24 hours. Finally, the addition of
lidocaine chlorhydrate has never caused patients any trouble. Another advantage
of using a non-obliterative solution is that the phlebectatic corona, a region
in which traditional sclerosing solutions are risky, can safely be injected.
T.R.A.P. begins “regeneration” where the thrust begins that allows the blood to
reach the right atrium. Moreover, it is interesting that sodium salicylate,
which is considered to be only of historical curiosity (34), when indeed it is
considered at all (36), should constitute a useful tool in the treatment of
venous insufficiency. Indeed, sodium salicylate possesses an essential
characteristic that is overlooked by most authors: it is not conducive to
hyperpigmentation (37, 38).

The methodical injection of all the vessels, which we regard as “gateways” to
the non-visible vessels, reduces the excessive capacity of the circulation,
improves the patient’s symptoms, corrects hemodynamic alterations and hinders
progression of the disorder. Today, transillumination enables us to pick out
many “gateways”, such as the tiny, more superficial perforating vessels, which
would otherwise be invisible . Moreover, it allows us to achieve even more rapid
and complete results, and to inject a smaller amount of solution for each single
injection. In T.R.A.P., short-term “recurrence” is not looked upon as failure,
as it is in obliterative sclerotherapy. The “recurrence” is caused by
hemodynamic factors and is a sign that the tributary vessels in the area have
not yet achieved sufficient continence. The appearance of a reticular vein
during regeneration is always useful, given that it constitutes a “gateway”
through which the non-visible vessels that have not yet been treated can be
reached. In such cases, the amount of solution injected is increased slightly.
In young patients with a familial predisposition to venous insufficiency.
T.R.A.P. can be used as a preventive measure. T.R.A.P. may also have an
exclusively functional value, in that just a few sessions, prior to the
application of bandages, are able to improve subjective symptoms in elderly
patients.

We also feel that the results of T.R.A.P. may help to change the attitude of
patients; we have already observed that patients are willing to undergo
treatment with a technique that is efficacious, yields good esthetic results and
is more respectful of the anatomy and functioning of the venous circulation in
the lower limbs. Indeed, all our patients have enjoyed a marked improvement in
their subjective symptoms as a result of the treatment. Moreover, echographic
examination reveals that the caliber of the vessels treated is reduced. We
believe that T.R.A.P. has the potential to be widely used. Indeed, alongside the
rigorously obliterative approach, there exists an orientation towards a milder
form of sclerotherapy that utilizes the minimal effective concentration of
solution (MSC), even when associated to the minimum volume(36). Clearly, a form
of sclerotherapy that is by definition obliterative cannot embrace our
philosophy. Indeed, “obliterating” the entire superficial and perforating
circulation is unthinkable; it can, however, be “regenerated”.
We commonly inject ******** solution even into the veins of the hands and
forearm , periocular venules, telangiectasias of the face (39), vascular
neoformations and, in very small quantities (a few drops) into spider naevi. As
the veins of the hands and forearm are less sensitive to the action of 6%
******** than those of the lower limbs, they can be reduced in caliber and
reinforced in one treatment session or in two sessions a month apart. Facial
telangiectasias, if they can be injected, are part of a three-dimensional
disorder.

The reduction in the overall volume of the veins reduces the hemodynamic
pressure on the capillary-papillary plexus, thereby enabling a more rapid and
stable result to be achieved through subsequent treatment by physical means,
which is always necessary in this region in order to eliminate the vessels
completely. By contrast, complete elimination of telangiectasias of the lower
limbs, in our experience, does not require the use of any physical technique.
The solution injected into the vessels of the cheek mainly flows toward the
mandible; only in the nasal and palpebral regions, therefore, do we apply
compression during injection of the angular vein at the internal corner of the
eyelid. Although the angular vein is normally valved, this maneuver is
recommended on account of the possibility of anatomical alterations of the
vessel.
For what concerns subcutaneous and submucosal venous angiomas, we first inject a
large quantity of 6% sodium salicylate in an alkaline hydroglycerin buffered
vehicle solution, followed by a powerful obliterative sclerosing solution, once
the vessels have been reduced.

Conclusions

The limits to three-dimensional regenerative ambulatory phlebotherapy will
only be established when the method is more widely used, more complex disorders
are treated and the results are monitored over a long period. At present,
however, the minimal invasiveness of the technique, its preservation of
anatomical integrity, its ease of execution, the high quality and persistence of
the results, the rapidity with which they are achieved, the absence of
complications and the satisfaction of the patients treated indicate that, in
terms of efficacy and safety, T.R.A.P. is far superior to any of the techniques
that we previously used.

Our intentions regarding Phlebotherapy

We are convinced that the validation of any phlebological treatment must
include photographic documentation of the patient before and after the
procedure. Tables, figures, diagrams and vague procedural hypotheses are
meaningless if no visual evidence of the result is provided. That this
subterfuge of not showing any proof of results has become the established common
practice during courses and congresses is, to say the least, alarming. Worse
still, this criticism also applies to phlebology publications, even to those
international journals such as Dermatologic Surgery (the official publication of
the American College of Phlebology) and Phlébologie. Indeed, leafing through
years of back-issues of these publications will not turn up a single verifiable
result of the therapies proposed! As a plastic surgeon, I judge this behaviour
to be highly questionable, at the very least. If, during our courses on
Timedsurgery or Elasticum face-lifting, we were unable to show the tangible
results of our operations, the participants would demand their money back, and
rightly so. Since the problem of therapeutic efficacy also concerns
three-dimensional regenerative phlebotherapy (T.R.A.P.), we intend to post on
this site the results of the most recent study on the efficacy of this
technique; the study terminated in July and the data are currently being
analysed. This double-blind study shows photographic proof of the results
achieved in 60 patients treated with a predetermined quantity of regenerative
solution in two sessions of phlebotherapy. In 20 cases, the photographic results
have been elaborated by means of pixel-count by the Faculty of Engineering of
the University of Genoa.

Acknowledgements

I wish to thank Silvia Perrella Segre, Bernard Patrick, Angela Sementa,
Aberto Cavalchini, Giovanni Levrero and Ottavio Cancelli, for their contribution
to this work